Search Results - EGA European Genome-phenome Archive

Testicular Cancer Consortium WES

We have leveraged our previous collaborative research to better understand the genetic underpinnings of testicular germ cell tumor (TGCT), and have completed whole exome sequencing on the DNA of patients at high risk for TGCT. Specifically, we conducted a study of high-risk individuals using data from Penn Medicine and the NCI. We collected germline DNA from blood or saliva samples from men with bilateral TGCT, and a family history consisting of at least one first to third degree relative diagnosed with the disease. The goal of the study was to identify coding genomic variation associated with predisposition to TGCT. Whole exome sequencing and gene burden analyses were performed on 293 men with a family history of TGCT or bilateral disease. 228 unique families were represented in this sample. Our results found a missense variant in the hinge domain of proto-oncogene PIM1. Several more candidates were identified via gene burden association, including loss-of-function variants in NIN and QRSL1. We also identified an association with variants in CFTR using gene-specific analysis. There was no association with sex and germ cell development pathways or regions identified by GWAS previously. We identified associations with three major pathways including, mitosis/cell cycle, co-translational protein targeting, and sex differentiation. Our results showed associations with variants in several genes, which suggests a multigenic heritability. We also found potential association with CFTR, co-translational protein targeting, and chromosomal segregation in sex determination. Our results suggest potential drug targets for TGCT prevention or treatment, e.g., PIM1, and the co-translational targeting pathway. To our knowledge, our study is the largest to date of men with high risk TGCT.

Study phs003107

Urine Cell-Free RNA Analysis for Cancer Detection and Therapy Response Prediction

The goal of this study was to develop a urine cell-free RNA (cfRNA) liquid biopsy assay for bladder cancer. We developed a method called uRARE-seq, which involves targeted RNA sequencing of urine cfRNA, and applied it to urine samples from bladder cancer patients and non-cancer controls. We evaluated its performance for bladder cancer detection and monitoring. We also developed a pre-treatment urine biomarker to predict the likelihood of response to intravesical therapy.

Study phs004116

National Cancer Institute (NCI) Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Colon, Kidney, Liver, Multiple Myeloma, and Prostate among Racially and Ethnically Diverse Populations

The Early Onset Malignancies Initiative (EOMI) is focused on collecting specimens from racially and ethnically diverse population groups with six different types of cancer (breast, prostate, colon, liver, kidney, and multiple myeloma). This initiative is a partnership between the Center for Research Strategy, the Center for Cancer Genomics and the Division of Cancer (DCP). DCP's NCI Community Oncology Research Program (NCORP) is a critical partner. The acquisition of the cancer and matching normal biospecimens in this initiative are from newly diagnosed early onset cancer patients who identify as Non-Hispanic Black, Hispanic, American Indian or Alaska Native, or Non-Hispanic White. The Minority/Underserved NCORPs sites will collect the samples for this project. By carrying out this initiative in the NCORP's national network of investigators, cancer care providers, and research institutions, the EOMI will harness the community-based partnerships to improve participation among these racial/ethnic groups. The NCORP investigators, as participants in NCI's clinical trials network, will annotate the biologic samples with clinical information that will enhance the ability to answer questions about molecular determinants of early disease, treatment response, and/or prognosis. The EOMI will be a step forward in addressing racial/ethnic disparities and in understanding cancer in underserved populations.

Study phs001952

NCTN: A Phase III Randomized Trial for Patients with De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients with High Allelic Ratio FLT3/ITD (AAML1031)

Study ID: AAML1031NCT Number: NCT01371981 Children's Oncology Group (COG)Submitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Phase III Randomized Trial for Patients with De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients with High Allelic Ratio FLT3/ITD (AAML1031)Trial Description: This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia. Clinical data presented in the following publication(s): PMID 32029509Disease type(s): Hematopoietic Neoplasm/Leukemia - Acute Myeloid LeukemiaClinical Dataset(s) included:NCT01371981-D4 (PMID 32029509): There is one dataset (-D4) for AAML1031's primary publication (PMID 32029509). This dataset is a patient level dataset which contains patient characteristics, consort diagram classifications, abnormal karyotype, CEBP alpha status, NPM status, minimal residual disease, survival, treatment-related mortality, and toxicity data presented in the manuscript for eligible pediatric acute myeloid leukemia (AML) patients enrolled on the AAML1031 clinical trial.Forthcoming Dataset(s): NCT01371981-D1, NCT01371981-D2, NCT01371981-D3, NCT01371981-D5, NCT01371981-D6You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004142

PCPT and SELECT Cohorts: Core Infrastructure Support for Cancer Research

SELECT study: SELECT was a phase III, double-blind, placebo-controlled 4-arm study of selenium, vitamin E, selenium and vitamin E together, and placebo designed to assess the effect of these supplements on the incidence of prostate cancer. Funded by the National Cancer Institute and conducted by SWOG, the study opened in August 2001 and quickly exceeded its accrual goal of 35,533 men.In the fall of 2008, the trial's Data Safety and Monitoring Committee recommended that participants discontinue taking study supplements due to convincing evidence (planned interim futility analysis) that neither vitamin E nor selenium supplements were associated with the prevention of prostate cancer. A subsequent analysis in 2011 showed a significant 17% increase in prostate cancer incidence in participants who were on the vitamin E only arm. Approximately 17,000 participants from the original trial recently completed an additional four years of centralized follow-up. This follow-up ended on May 31, 2014 and SELECT is now closed. PCPT study: The Prostate Cancer Prevention Trial (PCPT) was a SWOG Cancer Research Network-coordinated study designed to test whether the drug finasteride (Proscar®) would prevent prostate cancer in men ages 55 and older. This study was closed on June 24, 2003 because the study objective had been reached. The results of the study, which did find a preventive benefit for the drug, were published as "The Influence of Finasteride on the Development of Prostate Cancer," in the New England Journal of Medicine on July 17, 2003.

Study phs003382

Environmental Chemical Body Burden and Prospective Breast Cancer Risk in the Cancer Prevention Study-3 Cohort - CIDR

This study is focused on chemical body burden of per- and poly-fluoroalkyl substances (PFAS), and concomitant risk of developing invasive breast cancer during the menopausal transition. We hypothesized that elevated body-burden levels of these endocrine-disrupting chemicals (EDCs) will increase the risk of developing breast cancer, and that alterations of the methylome will link these chemical exposures and breast cancer. In Specific Aim 1, using samples and data from a prospective study of women in the American Cancer Society (ACS) Cancer Prevention Study 3 (CPS-3), we are assessing the association between body burden of PFAS during the menopausal transition and subsequent development of invasive breast cancer. The California Environmental Chemistry lab is determining PFAS levels in plasma samples collected 1 to 7 years prior to a diagnosis of invasive breast cancer from 998 ACS CPS-3 participants and 998 matched, cancer-free CPS-3 participants. All subjects were between 40 and 57 years of age when the blood sample was taken. In Specific Aim 2, studying the same participants, DNA methylation (DNAm) using Infinium MethylationEPIC BeadChips was conducted at Center for Inherited Disease Research (CIDR). We are conducting an epigenome-wide association study (EWAS) to identify DNAm changes associated with levels of PFAS in the cancer-free participants. We then will determine the association between the PFAS-associated DNAm changes and risk of developing breast cancer. The design is a nested case control study within the ACS CPS-3 cohort. Available data include the DNAm data and phenotypic data on case or control status, age at diagnosis of breast cancer, age at blood draw for cases and controls, and self-reported race/ethnicity.

Study phs003494

Comprehensive Genomic Characterization of Translocation Renal Cell Carcinoma

Xp11 translocation renal cell carcinoma (tRCC) is a rare, female-predominant cancer driven by a fusion between the TFE3 gene on chromosome Xp11.2 and a partner gene on either chrX or an autosome. It remains unknown what types of rearrangements underlie TFE3 fusions, whether fusions can arise from both the active (chrXa) and inactive X (chrXi) chromosomes, and whether TFE3 fusions from chrXi translocations account for the female predominance of tRCC. To address these questions, we performed haplotype-specific analyses of chrX rearrangements in tRCC whole genomes. We show that TFE3 fusions universally arise as reciprocal translocations and that oncogenic TFE3 fusions can arise from chrXi:autosomal translocations. Female-specific chrXi:autosomal translocations result in a 2:1 female-to-male ratio of TFE3 fusions involving autosomal partner genes and account for the female predominance of tRCC. Our results highlight how X chromosome genetics uniquely constrains somatic chrX alterations and underlies cancer sex differences.This version of the dbGaP study provides a comprehensive set of whole genome data and tables with clinical information collected for the 16 patients (15 pateints as tRCC and 1 patient as ccRCC) in the study cohort. The data also contains 12 RNA-seq samples used in the study and analyses. We anticipate that this data will considerably advance our molecular and genetic understanding of oncogenic translocations in TFE3-tRCC involving inactive chromosome X and its role in cancer sex bias.

Study phs003008

DNA-Sequencing of Baseline and Progression Plasma from the Phase III Alliance A031201 Trial

Circulating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We developed a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone. For the AR ctDETECT assay, DNA-seq libraries were constructed from cfDNA using Takara ThruPLEX Tag-Seq or Plasma-Seq kits, and subjected to hybridization enrichment using a custom-designed Agilent SureSelect bait panel. Post-capture DNA-seq libraries were pooled and sequenced on an Illumina HiSeq 2500 or an Illumina NovaSeq 6000 SP using 2x150 bp settings. ctDNA positivity was defined by samples harboring high ctDNA aneuploidy as measured by a modified ichorCNA algorithm, or samples harboring low ctDNA aneuploidy but displaying AR gain or genomic structural rearrangement (AR-GSR), MYC/MYCN gain, or a pathogenic mutation. We used the AR-ctDETECT assay to analyze plasma collected at baseline from 776 patients, and found that 59% were ctDNA-positive. Patients who were ctDNA-positive at baseline had significantly worse median overall survival than patients who were ctDNA-negative at baseline. We also used the AR-ctDETECT assay to analyze plasma collected at progression from 431 patients. Relative to baseline cfDNA, progression cfDNA exhibited enrichment of features associated with poor prognosis, including elevated cfDNA concentrations and increased ctDNA positivity. AR alterations were enriched at progression relative to baseline, primarily driven by AR-GSRs, including those predicted to truncate the AR ligand binding domain and originate from AR amplification on extrachromosomal DNA. Stratification by radiographic progression-free survival revealed that patients with rapid progression were enriched for non-AR gene alterations, while patients with initially durable responses showed selective enrichment of AR alterations. These results indicate that non-AR genetic alterations in ctDNA are associated with primary resistance to AR pathway inhibitors in first-line mCRPC, while AR alterations are associated with secondary resistance, even in patients who initially respond. .

Study phs003325

Personalized DNA and Peptide Vaccines Elicit Neoantigen-Driven T-Cell Responses in Pancreatic Cancer

This study provides data from two phase I clinical trials (NCT03122106, NCT03956056) that evaluated the safety and immunogenicity of DNA-based and synthetic long peptide personalized cancer vaccines. Exome and RNA sequence data were used to identify somatic mutations, predict neoantigens, and design personalized cancer vaccines. Immune monitoring was performed on each patient to assess neoantigen specific T-cell responses.

Study phs004463

Blood and Marrow Clinical Trials Network (BMT CTN) Comparing Peripheral Blood Stem Cell Transplantation versus Bone Marrow Transplantation in Individuals With Hematologic Cancers (0201) (BMT-CTN-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. ObjectivesTo compare survival rates of patients with hematologic cancers that received transplantation of granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) versus marrow from HLA-compatible unrelated donors.BackgroundMany studies of allogeneic marrow transplantation have shown that a higher dose of marrow cells correlates with a stronger hematopoietic engraftment and lower mortality from infectious complications. Peripheral blood stem cells (PBSC) collected after mobilization with granulocyte colony stimulating factor (G-CSF) contain a large number of CD34-positive progenitors and total cells than bone marrow. These observations led to the hypothesis that transplantation of PBSC would lead to lower mortality compared to transplantation of marrow. However, some studies have also shown increased risk of acute and chronic graft-versus-host disease (GVHD), as compared to bone marrow.Participants Between March 2004 and September 2009, 551 subjects were enrolled at 48 centers. Eligible subjects were less than 66 years of age and were planning to undergo transplantation for acute leukemia, myelodysplasia, chronic myeloid or myelomonocytic leukemia, or myelofibrosis. Design Subjects were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. Donors and recipients were DNA typed to ensure matching for 5 or 6 of the HLA-A, B, and DRB1 antigens. Peripheral-blood stem-cell donors were prescribed filgrastim or lenograstim at a dose of 10 μg per kilogram per day for 5 days and underwent apheresis. Recipients received one of four conditioning regimens and one of two GVHD prophylaxis regimens that were specified prior to randomization. Supportive care and treatment for GVHD were provided according to institutional standards. Subjects were followed in the study for 3 years. The primary end point was 2-year survival as assessed by means of an intention-to-treat analysis. Secondary end points included post-transplantation incidences of neutrophil and platelet engraftment, graft failure, acute and chronic GVHD, relapse, and infections. Conclusions There was no detected significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Further analysis indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD (Anasetti, C. et al., N Engl J Med. 2012).

Study phs004601

Somatic Mutation in Normal Bladder Study

Adult human somatic tissues are landscapes of mutant clones, but little is known about how these landscapes are shaped by known cancer risk factors. The goal of this study was to determine how the main bladder cancer risk factors (sex and smoking) change the mutational landscape of the normal urothelium. We collected normal urothelium from 45 donors at autopsy by brushing ~2cm² of the surface epithelium in the upper part (dome) and lower part (trigone) of the bladder (79 samples total). To identify mutations with high sensitivity we employed ultradeep (~5000x) DNA error-correcting duplex-sequencing on a panel of 15 protein coding genes and the TERT promoter, previously described to be under positive selection in normal urothelium or relevant to bladder cancer. We identified thousands of clonal driver mutations, which demonstrate pervasive positive selection in the normal urothelium. Males showed a significantly higher number of driver truncating mutations in RBM10, CDKN1A and ARID1A, despite similar rates of non-coding mutations, indicating stronger positive selection and clonal expansion in the male urothelium. We also discovered clonal expansions driven by activating TERT promoter mutations in the normal bladder, which were strongly associated with age and smoking. These results demonstrate that sex and smoking shape the clonal landscape of the normal bladder and indicate that the high mutational content of normal tissues might be leveraged to study the effect of mutations in vivo (i.e. natural saturation mutagenesis). We will deposit in dbGaP de-identified relevant clinical information from the 45 donors and the fastq files derived from duplex sequencing of the 79 samples in the study. We will also deposit fastq files derived from duplex sequencing of 3 control cord blood samples.

Study phs004105

BTC GBM TeamLab Trial 1: Longitudinal Tissue Profiling of Recurrent Malignant Glioma During Repeat Dosing of Oncolytic Viral Immunotherapy (NCT03152318)

The data in this repository is generated from the work of the GBM TeamLab as part of Break Through Cancer (BTC) (https://breakthroughcancer.org/). The TeamLab's goal is to evaluate the feasibility, safety, and value of performing serial brain biopsies to obtain biological readouts during the assessment of novel glibolastoma (GBM) therapeutics. The first investigational agent studied by the TeamLab is a novel oncolytic viral immunotherapy (agent: CAN-3110, also known as rQNestin34.5v.2) which was delivered via repeated intratumoral delivery at up to 6 timepoints over a 4-month period in recurrent IDH-wild type GBM patients. Biopsy tissues, blood, and CSF were collected and subjected to multi-omic profiling at each surgical timepoint. This work is being conducted as one of the trial arms for NCT03152318. Controlled access omic data from this study will be deposited here as the results are published.

Study phs004189

Transcriptomic Profiling of Peripheral Immune Cells in a Trial of Ruxolitinib with Nivolumab for Anti-PD1 Non-Responsive cHL

Treatment with checkpoint inhibitors is effective in multiple cancer types. However, even in cancers with high response rates such as Hodgkin lymphoma, some patients fail to respond or relapse following an initial response to checkpoint inhibitors. In this study, we examined patients enrolled in a clinical trial of ruxolitinib with nivolumab in relapsed or refractory Hodgkin lymphoma (NCT03681561). Patients relapsed or refractory to anti-PD1 therapy received ruxolitinib for 8 days followed by nivolumab every 4 weeks and continued ruxolitinib twice daily. For this transcriptomic study, peripheral blood mononuclear cells (PBMCs) were collected at baseline and 8 days of ruxolitinib therapy and analyzed by single-cell and bulk RNA-sequencing.

Study phs003601

Epigenetic Control of Topoisomerase 1 by MacroH2A1.1

DNA transactions introduce torsional constraints that pose an inherent risk to genome integrity. While topoisomerase 1 (TOP1) activity is essential for removing DNA supercoiling, aberrant stabilization of TOP1:DNA cleavage complexes (TOP1ccs) can result in cytotoxic single-stranded DNA lesions (SSLs). What protects the genome from aberrant TOP1 activity remains unknown. Using a combination of CUT&RUN and TOP1 Covalent Adduct Detection (CAD) Seq in MDA-MB-231 breast cancer cells (American Type Culture Collection, ATCC), we identified chromatin context as an essential means to ensure TOP1cc resolution at TOP1 hot spots. Through its ability to bind poly(ADP-ribose) (PAR), a protein modification required for TOP1cc repair, the histone variant macroH2A1.1 establishes a TOP1-permissive chromatin environment, while the alternatively spliced macroH2A1.2 isoform is unable to bind PAR or protect from TOP1ccs. MacroH2A1 isoform-specific analyses were based on reconstitution of macroH2A1.1 knockout cells with wild-type or PAR binding-deficient FLAG-tagged macroH2A1.1 in human breast cancer cells. Mechanistically, we find that macroH2A1.1 facilitates the recruitment of the TOP1cc repair factor XRCC1 in response to both endogenous and drug-induced topological stress. Impaired macroH2A1.1 splicing, a frequent cancer feature, was predictive of increased sensitivity to TOP1 poisons in a pharmaco-genomic screen in breast cancer cells, and macroH2A1.1 inactivation mirrored this effect in breast and ovarian cancer cells. Consistent with this, low macroH2A1.1 expression correlated with improved survival in cancer patients treated with TOP1 inhibitors (TOP1i). We propose that macroH2A1 alternative splicing serves as an epigenetic modulator of TOP1-associated genome maintenance and a potential cancer vulnerability.

Study phs003729

Women's Health Initiative Clinical Trial and Observational Study - Imaging

Objectives: The clinical trial assessed the safety and efficacy of three interventions. Specifically, it evaluated (1) the major health benefits and risks of estrogen plus progestin and estrogen alone, (2) the effects of a low-fat eating pattern on risk of colorectal cancer, and (3) the efficacy of calcium with vitamin D supplementation for preventing hip and other fractures. The objective of the memory study was to determine whether estrogen plus progestin therapy protects global cognitive function, and evaluate the therapy's effect on the incidence of dementia and mild cognitive impairment.The observational study is examining the relationship between lifestyle, socioeconomic, health, and other risk factors with cardiovascular, breast cancer, colorectal cancer and osteoporotic fracture outcomes. Secondary objectives include providing more reliable estimates of the extent to which known risk factors predict disease, more precise estimates of new occurrences of disease, and to provide a future resource for the identification of new or novel risk factors especially factors found in blood. Background: The Women's Health Initiative (WHI) is a long-term national health study that has focused on strategies for preventing the major causes of death, disability, and frailty in postmenopausal women, specifically heart disease, cancer, and osteoporotic fractures. The WHI is primarily composed of an observational study (OS), as well a clinical trial (CT) with three components: Hormone Replacement Therapy (HT), Dietary Modification, (DM) and Calcium/Vitamin D supplementation (CaD).Prior to the WHI, observational studies suggested that postmenopausal hormone therapy was associated with a decreased risk of coronary heart disease (CHD). Potential cardioprotection was based on generally supportive data on lipid levels in intermediate outcome clinical trials, trials in nonhuman primates, and a large body of observational studies suggesting a 40% to 50% reduction in risk among users of either estrogen alone or, less frequently, combined estrogen and progestin. Observational studies primarily examining unopposed estrogen preparations have suggested a 30% to 50% reduction in coronary events, and an 8% to 30% increase in breast cancer with extended use. Other research findings indicated that hormone therapy was also associated with a decreased risk of osteoporosis and increased bone density. The WHI HT trials were designed to test the effects of postmenopausal hormone therapy on risk for coronary heart disease and assess overall risks and benefits in predominantly healthy women. The Women's Health Initiative Memory Program (WHIMS) consists of a suite of studies which include cohorts of women who participated in the WHI HT trials. Postmenopausal women have a greater risk than men of developing Alzheimer's disease, but studies of the effects of estrogen therapy on Alzheimer's disease have been inconsistent. Additionally, observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. International comparisons and migration studies have suggested that countries with 50% lower fat intake than the US population had approximately one third the risk of colorectal cancer. Additionally, fairly consistent evidence existed for an effect of dietary fat, vegetables and fruits, and grains on colorectal cancer risk from within-country observational studies, although the protective effect of lower fat intake was no longer clear after adjusting for energy intake. The WHI DM trial was the first randomized trial to directly address the health effects of a low-fat eating pattern in predominantly healthy postmenopausal women from diverse racial/ethnic, geographic, and socioeconomic backgrounds. Osteoporosis is a major cause of injury, loss of independence, and death, and contributes to hip fractures. Observational evidence and data from previous randomized clinical trials suggest that calcium and/or vitamin D supplements may slow bone loss and reduce the risk of falls in postmenopausal and elderly women. However, evidence from trials, observational studies, and meta-analyses of calcium and vitamin D supplementation with respect to hip and other fractures was limited at the time the WHI was initiated. In two prior randomized trials, calcium plus vitamin D supplements did not reduce the risk of nonvertebral fractures among older women. When the WHI CaD trial was designed, guidelines recommended daily intakes of 800 to 1200 mg of calcium with 400 IU of vitamin D for the prevention of osteoporosis, which was not met by many American women. Therefore, the WHI CaD trial was designed to test the primary hypothesis that postmenopausal women randomly assigned to calcium plus vitamin D supplementation would have a lower risk of hip fracture and, secondarily, of all fractures than women assigned to placebo. Subjects: Postmenopausal women ages 50 to 79 were eligible to participate. A woman was considered postmenopausal if she had experienced no vaginal bleeding for 6 months (12 months for women under 55 years of age), had had a hysterectomy, or had ever used postmenopausal hormones. Recruitment was carried out in 40 US clinical centers in 1993-1998. The clinical trial components had additional specific inclusion or exclusion criteria.A total of 68,132 women were randomized into at least one component of the clinical trial. 27,347 women were enrolled in the hormone therapy component with 16,608 in the estrogen plus progestin trial and 10,739 in the unopposed estrogen trial, 48,835 women were enrolled in the diet modification component, and 36,282 women were enrolled in the calcium/vitamin D component. 7,479 women 65 years of age and older at baseline and that participated in the HT trial component were enrolled in the ancillary memory study. Women who were either ineligible or unwilling to participate in the clinical trial component were enrolled in the observational study. For example, many potential participants to the clinical trial component of the study were already undertaking a low fat diet or were using hormone replacement therapy. The effect of the selection process was that women enrolled in the observational study tended to have healthier lifestyles compared to those enrolled in the clinical trial. In total, 93,676 subjects were enrolled in WHI OS, with over 16% being members of a racial/ethnic minority group. The first WHI Extension Study enrolled 115,407 consenting participants from all components of the original WHI study for an additional five years of follow-up, from 2005 to 2010. In 2010, 93,567 women consented to continued follow-up. Design: The clinical trial component of the WHI included three randomized comparisons: hormone therapy, dietary modification, and calcium/vitamin D supplementation. Women could have been randomized into one, two or all three trials.The hormone therapy trial enrolled women to one of two double-blinded trials: estrogen (0.625 mg of conjugated equine estrogens daily) plus progestin (2.5 mg of medroxyprogesterone acetate daily) or estrogen alone. Women with a prior hysterectomy were eligible for the trial of unopposed estrogen. Women with an intact uterus at screening were initially also eligible for unopposed estrogen, but were reassigned to the trial of combined postmenopausal hormones beginning in 1995. Both trials randomized participants 1:1 to either hormone therapy or placebo. A 3-month washout period was required before baseline evaluation of women using postmenopausal hormones at initial screening. Study participants were contacted by telephone 6 weeks after randomization to assess symptoms and reinforce adherence. Follow-up contacts by telephone or clinic visit occurred every 6 months, with clinic visits required annually. The estrogen plus progestin trial was halted in July 2002 after a mean 5.2 years of follow-up because health risks, including increased risk of breast cancer and cardiovascular disease, exceeded benefits. The estrogen alone trial was stopped early in March 2004, because an increased risk of stroke was found with no benefit for coronary heart disease. The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. The dietary modification trial evaluated the effect of a low-fat, high fruit, vegetable, and grain diet on preventing cardiovascular disease and cancer. Participants were randomly assigned to an intervention or a comparison group in the ratio of 2:3 for cost-efficiency. The intervention was an intensive behavioral modification program, using 18 group sessions in the first year and quarterly sessions thereafter, led by specially trained and certified nutritionists. The program was designed to promote dietary change with the goals of reducing total fat to 20% of energy intake, increasing vegetables and fruits to at least 5 servings daily and grains to at least 6 servings daily. The intervention did not include total energy reduction or weight loss goals. Comparison group participants received a copy of the US Department of Health and Human Services' Dietary Guidelines for Americans and other health-related materials but were not asked to make dietary changes. Dietary intake was monitored using the WHI food frequency questionnaire at 1 year and in a rotating one-third subsample every year thereafter. Women completed a medical update questionnaire every 6 months, and medical records were sought for all women reporting colorectal cancer. The primary outcome was invasive colorectal cancer incidence. Participants in the calcium/vitamin D trial were randomized 1:1 to either supplements or placebo. Active tablets contained 500 mg of elemental calcium (as calcium carbonate) and 200 IU of vitamin D3, to be taken twice daily with meals. The presence and severity of symptoms, safety concerns, and outcomes were ascertained at annual clinic visits and telephone or clinic visits at intervening six-month intervals. Risk factors for fracture were assessed by questionnaire, interview, and clinical examination. The primary outcome was incidence of hip fracture. Participants in the observational study attended a baseline examination and were re-examined three years later. Participants completed annual updates of exposures and clinical outcomes by mail. Final data were collected by mail during the close-out period in April 2004 to March 2005. The major clinical outcomes of interest were coronary heart disease, stroke, breast cancer, colorectal cancer, endometrial cancer, ovarian cancer, osteoporotic fractures, diabetes, and total mortality. Most outcomes were initially ascertained by self-report on an annual questionnaire and documented by hospital and related records. Charts with potential cardiovascular, cancer, and fracture outcomes were sent to the local physician adjudicator for evaluation and classification. Staff at the Clinical Coordinating Center coded and adjudicated all cancers of major interest in the study using standardized SEER guidelines. In 2005, WHI participants were invited to join the Extension Study for an additional five years of follow-up in order to collect long-term outcomes. Participants completed annual data collection forms primarily by mail, similar to the OS follow-up. Women reporting study outcomes were contacted by WHI field center staff to obtain additional details and medical records, which were evaluated by physician adjudicators. In 2010, the woman remaining were invited to join the next Extension Study. In the second extension, women were divided into two groups, one of which would have outcomes documented with medical records (the Medical Records Cohort, MRC), and the other would just be followed by self-report (the Self-Report Cohort, SRC). The MRC consists of women who were in the hormone therapy trials, and all African-American and Hispanic women. In 2012-2013, a subset of the MRC was identified for a potential in-home visit to collect blood and several objective measures of physical functioning. Conclusions: Overall health risks exceeded benefits from use of combined estrogen plus progestin after an average 5.2 year follow-up among healthy postmenopausal US women (Rossouw et al., 2002, PMID:12117397). Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo (Rapp et al., 2003, PMID: 12771113), increased the risk for probable dementia, and did not prevent mild cognitive impairment (Shumaker, et al., 2003, PMID: 12771112). The use of conjugated equine estrogen increased the risk of stroke, decreased the risk of hip fracture, and did not affect CHD incidence in postmenopausal women with prior hysterectomy after an average of 6.8 years of follow-up (Anderson et al., 2004, PMID: 15082697). Over approximately 8 years of follow-up, a low-fat dietary pattern did not reduce the risk of colorectal cancer (Beresford, et al., PMID: 16467233). Calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density; however, no significant difference was observed in hip fractures (Jackson, et al., 2006, PMID: 16481635). A recent review summarizes the conclusions from the WHI clinical trials with a focus on clinical practice (Manson, et al., 2024, PMID: 38691368).Description of ECG Imaging Data: Electric cardiograms (ECGs) were given to all clinical trial participants at baseline and in years 3, 6, and 9 of the original WHI study.EKG data consist of 12 lead 10 seconds ECGS sampled at 500Hz via GE ECG machines and process via GE MUSE system. The ECG waveform were directly exported from GE MUSE using MUSE export function in XML format, which include EKG waveform data as well as other ECG characteristics. Waveform data is in base64 encoded format, when it is decoded, it is a binary data that can be used to draw waveform graph. Many programming languages and data tools have built in functions to decode base64 strings. All the other necessary information is included in the LeadData section, total byte size, total sample size etc. (usually 1 sample is 2 bytes). See example below: encoded-data (base64 encoded string) JwAoAC0AKAAiACIAJAAkACQAIwAiACIAHgAcABwAGwAZABgAGAAYABcAEwAQABAAEAAL^/AAsADAAM... decoded-binary-data (1 sample is 2 bytes) 270028002D002800220022002400240024002300220022001E001C001C001B00 1900180018001800170013001000100010000B000B000C000C000D000D000D00 0A000A000A0009000600040004000700070005000500020... These binary values are integers (Y axis data of the graph), hence it is a straightforward process to draw the waveform graph. Acquisition dates have been redacted from this ECG data to comply with WHI policy. All acquisition dates within files and in file names have been set to January 1, 1900 (19000101) to comply with this policy.

Study phs003824

Immediate Postoperative Minimal Residual Disease Detection with MAESTRO Predicts Recurrence and Survival in Head and Neck Cancer Patients Treated with Surgery

We selected 24 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who were surgically treated. MAESTRO, our ultrasensitive, tumor-informed, mutation enrichment sequencing assay, was applied in a pooled format (MAESTRO-Pool) to plasma samples collected from these patients at baseline (pre-op) and postoperatively. We show that detection of circulating tumor DNA (ctDNA) 1 to 9 days after surgery is associated with significantly worse survival. Many plasma samples also had tumor fractions detected below 100 parts-per-million, the detection limit for first-generation commercial assays, highlighting the need for more sensitive ctDNA assays. Here we provide whole genome sequencing of matched tumor biopsy and normal germline DNA from 24 patients that were used to identify somatic single nucleotide variants (SNVs) to be tracked using our MAESTRO-Pool assay.

Study phs003981

NCTN: A Randomized Phase III Trial of CC-5013 (Lenalidomide) and Low Dose Dexamethasone (LLD) versus Bortezomib, Lenalidomide and Low Dose Dexamethasone (BLLD) for Induction, in Patients with Previously Untreated Multiple Myeloma (S0777)

Study ID: S0777NCT Number: NCT00644228 SWOG Cancer Research NetworkSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Randomized Phase III Trial of CC-5013 (Lenalidomide) and Low Dose Dexamethasone (LLD) versus Bortezomib, Lenalidomide and Low Dose Dexamethasone (BLLD) for Induction, in Patients with Previously Untreated Multiple Myeloma (S0777)Trial Description: This randomized phase III trial studies lenalidomide, dexamethasone, and bortezomib to see how well it works compared to dexamethasone and lenalidomide alone in treating patients with previously untreated multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. It is not yet known whether lenalidomide and dexamethasone is more effective with or without bortezomib in treating multiple myeloma. Data presented in the following publication(s): PMID 28017406Disease type(s): Hematopoietic Neoplasm/Myeloma - MyelomaClinical Dataset(s) included:NCT00644228-D1 (PMID 28017406): There are two datasets for S0777's primary publication 28017406 (-D1 and -D2). This dataset, NCT00644228_D1.txt, contains data included in the aforementioned publication, which included primary and secondary efficacy results evaluating the addition of bortezomib to lenalidomide and low dose dexamethasone induction therapy for the treatment of patients with newly diagnosed multiple myeloma in the SWOG phase III trial, S0777. The dataset includes baseline characteristics, treatment discontinuation reasons, stratification factors, survival, outcome, second primary cancer, and FISH data.NCT00644228-D2 (PMID 28017406): There are two datasets for S0777's primary publication 28017406 (-D1 and -D2). This dataset, NCT00644228_D2.txt, contains data for the safety analyses included in the aforementioned publication, which compared toxicity between bortezomib, lenalidomide and low dose dexamethasone versus lenalidomide and low dose dexamethasone induction therapy for the treatment of patients with newly diagnosed multiple myeloma in the SWOG phase III trial, S0777.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004247

Genomic Characterization CS-MATCH-0007 Arm P

The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm P is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with PTEN loss by IHC are treated with the drug GSK2636771. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

Study phs002152

The Oral Microbiome and Head and Neck Cancer

Oral microbiota may influence head and neck squamous cell carcinoma (HNSCC) development, potentially related to carcinogen metabolism. The human oral cavity hosts a diverse microbiota, including bacteria and fungi. We performed shotgun sequencing and ITS1 sequencing on 236 HNSCC case participants who developed HNSCC during a mean follow-up of 5.1 years and 458 matched controls who remained HNSCC-free. Oral samples were obtained from a prospective nested case-control study within three epidemiological cohorts: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (ACS CPS-II), the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the Southern Community Cohort Study (SCCS). Control participants were selected using 2:1 frequency matching based on cohort, age, sex, race and ethnicity, and time since oral sample collection.

Study phs004018

NCTN: A Randomized Trial of Axillary Node Dissection in Women With Clinical T1-2 N0-1 M0 Breast Cancer Who Have a Positive Sentinel Node (ACOSOG-Z0011)

Study ID: ACOSOG-Z0011NCT Number: NCT00003855 Alliance for Clinical Trials in OncologySubmitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: A Randomized Trial of Axillary Node Dissection in Women with Clinical T1-2 N0-1 M0 Breast Cancer Who Have a Positive Sentinel Node (ACOSOG-Z0011)Trial Description: RATIONALE: Surgery to remove lymph nodes in the armpit may remove cancer cells that have spread from tumors in the breast.PURPOSE: Randomized phase III trial to determine the effectiveness of removing lymph nodes in the armpit in treating women who have stage I or stage IIA breast cancer.Clinical data presented in the following publication(s):PMID 21304082 Disease type(s): Breast Neoplasm - Breast Neoplasm, MiscellaneousClinical dataset(s) included:NCT00003855-D1 (PMID 21304082): There is one dataset associated with the primary analysis publication (PubMed ID: 21304082) for study NCT00003855. This dataset contains baseline characteristics, treatment arm, lymph node surgery information, estrogen and progesterone receptor status, and recurrence and survival data.You are encouraged to view the PDF data dictionaries found in the "Documents" tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004234

Center for Cancer Genomics (CCG) Cancers of Unknown Primary Project (CUPP)

The Cancers of Unknown Primary Project (CUPP) aims to characterize difficult tumor types with the goal of determining future best treatment practices. NCI will utilize whole exome sequencing, copy-number variation, DNA methylation in conjunction with transcriptome sequencing to provide a comprehensive genomic landscape of Cancers of Unknown Primary (CUP). The samples will be processed and submitted for genomic characterization using pipelines and procedures established within the Center for Cancer Genomics (CCG).

Study phs001801

Derivation of Doxorubicin Mutational Signatures in Cancer

Study design and aims: This study utilizes doxorubicin exposed cell lines to derive doxorubicin mutational signatures. To validate the methodology used (bulk whole-genome sequencing of cells exposed to drug with a pulsed dose-escalation approach), cisplatin mutational signatures are first derived and compared to previously published data (single constant dose of drug and whole-genome sequencing of single-cell clones). The primary aim of the study was to characterize the impact of doxorubicin mutagenesis on the genome. Furthermore, to assess the presence of derived doxorubicin signatures in patient samples treated with a doxorubicin-containing regimen. Population information: The study utilizes atypical teratoid rhabdoid tumor (ATRT) (n=2) and renal medullary carcinoma (RMC) (n=2) cell lines. To acquire cisplatin and doxorubicin exposed cells, parental cells were treated with escalating doses of cisplatin and doxorubicin in a pulsed manner for between 2-12 months. This study also contains 2 cell lines derived from one patient with metastatic disease, treated with a doxorubicin-containing regimen. Molecular technologies: Whole-genome sequencing of the bulk cell population.Principal findings: Cisplatin mutational signatures were consistent with previously published data. This study identified two related single-base substitution (SBS) doxorubicin mutational signatures. While the two resulting signatures had some similarities, they differed in their frequencies of C > A (SBS-Doxorubicin-1) and T > C (SBS-Doxorubicin-2) substitutions. A double-base substitution (DBS) signature was also observed in association with SBS-Doxorubicin-2. This DBS signature harbored peaks at TG > CA, TG > GT, and TT > CC substitutions. Next, two INDEL signatures were derived. The first consisted of 1bp insertions and deletions at T homopolymers, >=2bp insertions at repetitive DNA, and microhomology deletions. The second consisted of >=2bp insertions at non-repetitive regions. Finally, both SBS-Doxorubicin signatures were found to be significantly present in patient samples exposed to a doxorubicin-containing regimen. Data Available through dbGaP: This dataset contains paired-end whole genome sequencing of parental (n=4), cisplatin exposed (n=2), and doxorubicin exposed (n=4) SMARCB1-deficient cell lines, as well as cell lines derived from one patient with metastatic disease (n=2), where the patient was treated with a doxorubicin-containing regimen.

Study phs004740

NCTN: A Phase III Randomized Study of Nivolumab Plus Ipilimumab versus Nivolumab for Previously Treated Patients with Stage IV Squamous Cell Lung Cancer and No Matching Biomarker (Lung-Map Sub-Study) (S1400I)

Study ID: S1400INCT Number: NCT02785952SWOG Cancer Research NetworkSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Phase III Randomized Study of Nivolumab plus Ipilimumab versus Nivolumab for Previously Treated Patients with Stage IV Squamous Cell Lung Cancer and No Matching Biomarker (Lung-Map Sub-Study) (S1400I)Trial Description: This randomized phase III trial compares nivolumab with ipilimumab and nivolumab alone in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a "non-match" sub-study that includes all screened patients not eligible for a biomarker-driven sub-study. Monoclonal antibodies, such as nivolumab and ipilimumab, may be able to shrink tumors. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with squamous cell lung cancer. Clinical data presented in the following publication(s):PMID 34264316 Disease type(s): Lung, Mediastinal and Pleural Neoplasm - Non-Small Cell Lung CancerClinical Dataset(s) included:NCT02785952-D1 (PMID 34264316): There are three datasets (-D1 through -D3) for PMID 34264316, a primary publication for S1400I. This clinical dataset, NCT02785952-D1, contains patient-level data (one row per patient), including baseline, demographic, metastatic sites, and treatment information. It also contains assessment, survival, reasons for going off treatment, tumor mutational burden, PDL1 expression, and patient-reported outcome data.NCT02785952-D2 (PMID 34264316): There are three datasets (-D1 through -D3) for PMID 34264316, a primary publication for S1400I. This toxicity dataset, NCT02785952-D2, contains event-level data (one row per patient per adverse event experienced on trial).NCT02785952-D3 (PMID 34264316): There are three datasets (-D1 through -D3) for PMID 34264316, a primary publication for S1400I. This dataset, NCT02785952-D3, contains biomarker data (one row per patient per gene alteration).You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004242

DNA Methylation in Prostate Tumor and Paired Benign Tissue for African and European Ancestry Men

We recruited prostate cancer (PCa) patients undergoing robotic-assisted laparoscopic radical prostatectomy at the University of Chicago Medical Center Urology Clinic between 2011 and 2017. Our study includes 76 African American (AA) and 75 European American (EA) men with PCa of Gleason Score (GS) ≥7, recruited by the Epidemiology Research Recruitment Core at the University of Chicago. All patients consented to the collection of questionnaire data, prostate tissue, and medical records. The study was approved by the Institutional Review Board of the University of Chicago. Following prostatectomy, prostate tissue was sent to the Human Tissue Research Center (HTRC) at the University of Chicago. Each sample underwent histological examination and Gleason scoring by University of Chicago genitourinary pathologists. The presence of adenocarcinoma was confirmed by overexpression of alpha-methylacyl-coenzyme-A racemase (AMACR) and areas for DNA extraction were marked. Tissue samples used for DNA extraction were obtained using with either a 1mm biopunch or laser microdissection of a 100 µm2 area of tissue. Genome-wide DNA methylation profiles were generated using Illumina's Infinium MethylationEPIC BeadChip array kit. Genome-wide SNP data was generated (from benign tissue DNA) using the Illumina Infinium Multi-Ethnic Global-8 v1.0 array at the University of Chicago Genomics Core Facility. We performed imputation using the Haplotype Reference Consortium (HRC, Version r1.1 2016) panel, which includes all samples from the 1,000 Genomes Project (Phase 3), using the Michigan Imputation Server. The imputed SNP data for mQTL analysis was imputed based on genotype SNP data which was all from benign tissue DNA and the methylation data was identified in both tumor and benign tissue, both AA and EA men, and identified QTLs co-occuring with prostate cancer susceptibility loci.Data including SNP genotypes, DNA methylation, tissue type, and participant characteristics will be available in dbGaP.

Study phs003516

NCTN: Dexamethasone Compared with Prednisone During Induction Therapy and Methotrexate with or without Leucovorin During Maintenance Therapy in Treating Patients with Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (AALL0232)

Study ID: AALL0232NCT Number: NCT00075725 Children's Oncology Group (COG)Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: Dexamethasone Compared with Prednisone during Induction Therapy and Methotrexate with or without Leucovorin during Maintenance Therapy in Treating Patients with Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (AALL0232)Trial Description: This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia (ALL). Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia. Clinical data presented in the following publication(s):PMID 27114587Disease type(s): Hematopoietic Neoplasm/Leukemia - Acute Lymphoblastic LeukemiaClinical Dataset(s) included:NCT00075725-D1 (PMID 27114587): There are three datasets associated with this publication (NCT00075725-D1, NCT00075725-D2, and NCT00075725-D3): NCT00075725-D1 includes all patients enrolled on the study. This dataset contains baseline characteristics, BCR-ABL fusion status, MLL rearrangement, bone marrow status at end of induction, and survival data.NCT00075725-D2 (PMID 27114587): There are 3 datasets associated with this publication (NCT00075725-D1, NCT00075725-D2, and NCT00075725-D3). NCT00075725-D2 is the subset of patients included in the randomized comparison between Capizzi and High-dose Methotrexate. The dataset includes baseline characteristics, BCR-ABL fusion status, MLL rearrangement, bone marrow status at end of induction, and survival data. Outcomes (EFS time, EFS indicator) in this dataset are different from the outcomes in NCT00075725-D1. The outcome of those assigned to Capizzi who subsequently received High-dose Methotrexate was censored at time of therapy crossover, since in AALL0232, therapy changes were recommended to provide HD-MTX to all participants who had not yet completed maintenance course 1 or received cranial irradiation.NCT00075725-D3 (PMID 27114587): There are three datasets associated with this publication (NCT00075725-D1, NCT00075725-D2, and NCT00075725-D3). NCT00075725-D3 is the toxicity data observed in the randomized cohorts (steroid and methotrexate).Additional whole genome genotyping data for this trial is available under phs001350.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004039

6048 results for "canc*"

in 42.54 milliseconds.